Reproductive - First Aid

Question 1

Important Genes of Embryogenesis:

• produced at base of limbs in zone of polarizing activity
• involved in patterning along anteroposterior axis and CNS development
• mutation can cause holoprosencephaly

Answer 1

Sonic Hedgehog Gene

Question 2

Important Genes of Embryogenesis:

• produced at apical ectodermal ridge (thickened ectoderm at distal end of each developing limb)
• necessary for proper organization along dorsal-ventral axis

Answer 2

Wnt-7 Gene

Question 3

Important Genes of Embryogenesis:

• produced at apical ectodermal ridge
• stimulates mitosis of underlying mesoderm, providing for lengthening of limbs

Answer 3

Fibroblast Growth Factor (FGF) Gene

“Look at that Fetus, Growing Fingers.”

Question 4

Important Genes of Embryogenesis:

• involved in segmental organization of embryo in a craniocaudal direction
• code for transcription factors
• mutations → appendages in wrong locations

Answer 4

Homeobox (Hox) Genes

Question 5

Early Embryonic Development

Answer 5

Question 6

Early Fetal Development:

hCG secretion begins around the time of implantation of blastocyst

Answer 6

Week 1

Blastocyst “sticks” at day 6.

Question 7

Early Fetal Development:

bilaminar disc (epiblast, hypoblast)

Answer 7

Week 2

2 weeks = 2 layers

Question 8

Early Fetal Development:

• gastrulation forms trilaminar embryonic disc
• cells from epiblast invaginate → primitive streak → endoderm, mesoderm, ectoderm
• notochord arises from midline mesoderm
• overlying ectoderm becomes neural plate

Answer 8

Week 3

3 weeks = 3 layers

Question 9

Early Fetal Development:

• neural tube formed by neuroectoderm and closes by week 4
• organogenesis
• extremely susceptible to teratogens

Answer 9

Weeks 3–8

(Embryonic Period)

Question 10

Early Fetal Development:

• heart begins to beat
• upper and lower limb buds begin to form

Answer 10

Week 4

4 weeks = 4 limbs and 4 heart chambers

Question 11

Early Fetal Development:

fetal cardiac activity visible by transvaginal ultrasound

Answer 11

Week 6

Question 12

Early Fetal Development:

fetal movements start

Answer 12

Week 8

Gait at week 8.

Question 13

Early Fetal Development:

genitalia have male/female characteristics

Answer 13

Week 10

tenitalia

Question 14

Embryologic Derivatives:

external/outer layer

Answer 14

Ectoderm

Question 15

Ectoderm:

• epidermis
• adenohypophysis (from Rathke pouch)
• lens of eye
• epithelial linings of oral cavity, sensory organs of ear, and olfactory epithelium
• anal canal below the pectinate line
• parotid, sweat, and mammary glands
• Craniopharyngioma
  
  • benign Rathke pouch tumor with cholesterol crystals, calcifications

Answer 15

Surface Ectoderm

Question 16

Ectoderm:

• brain (neurohypophysis, CNS neurons, oligodendrocytes, astrocytes, ependymal cells, pineal gland)
• retina
• spinal cord

Answer 16

Neural Tube

Question 17

Ectoderm:

• melanocytes
• myenteric (Auerbach) plexus
• odontoblasts
• endocardial cushions
• laryngeal cartilage
• parafollicular cells of the thyroid
• PNS (dorsal root ganglia, cranial nerves, autonomic ganglia)
• adrenal medulla and all ganglia
• spiral membrane (aorticopulmonary septum)
• Schwann cells
• pia and arachnoid
• bones of skull

Answer 17

Neural Crest

MMOtEL PPASS:

• Melanocytes
• Myenteric (Auerbach) plexus
• Odontoblasts
• Endocardial cushions
• Laryngeal cartilage
• Parafollicular cells of the thyroid
• PNS (dorsal root ganglia, cranial nerves, autonomic ganglia)
• Adrenal medulla and all ganglia
• Spiral membrane (aorticopulmonary septum)
• Schwann cells

Question 18

Embryologic Derivatives:

• muscle, bone, connective tissue, serous linings of body cavities (eg. peritoneum, pericardium, pleura), spleen (derived from foregut mesentery), cardiovascular structures, lymphatics, blood, wall of gut tube, upper vagina, kidneys, adrenal cortex, dermis, testes, ovaries
• notochord induces ectoderm to form neuroectoderm (neural plate)
• its only postnatal derivative is the nucleus pulposus of the intervertebral disc

Answer 18

Mesoderm

middle/“meat” layer

Mesodermal Defects = VACTERL:

• Vertebral defects
• Anal atresia
• Cardiac defects
• Tracheo-Esophageal fistula
• Renal defects
• Limb defects (bone and muscle)

Question 19

Embryologic Derivatives:

• gut tube epithelium (including anal canal above the pectinate line)
• most of urethra and lower vagina (derived from urogenital sinus)
• luminal epithelial derivatives (eg. lungs, liver, gallbladder, pancreas, eustachian tube, thymus, parathyroid, thyroid follicular cells)

Answer 19

Endoderm

Question 20

Types of Errors in Morphogenesis:

absent organ due to absent primordial tissue

Answer 20

Agenesis

Question 21

Types of Errors in Morphogenesis:

absent organ despite presence of primordial tissue

Answer 21

Aplasia

Question 22

Types of Errors in Morphogenesis:

• incomplete organ development
• primordial tissue present

Answer 22

Hypoplasia

Question 23

Types of Errors in Morphogenesis:

2° breakdown of previously normal tissue or structure (eg. amniotic band syndrome)

Answer 23

Disruption

Question 24

Types of Errors in Morphogenesis:

• extrinsic disruption
• occurs after embryonic period

Answer 24

Deformation

Question 25

Types of Errors in Morphogenesis: * intrinsic disruption * occurs during embryonic period (weeks 3–8)

Answer 25

Malformation

Question 26

Types of Errors in Morphogenesis: abnormalities result from a single 1° embryologic event (eg. oligohydramnios → Potter sequence)

Answer 26

Sequence

Question 27

\_\_\_\_\_ are agents or factors that causes malformation of an embryo. Most susceptible in 3rd–8th weeks (embryonic period—organogenesis) of pregnancy. Before week 3, “all-or-none” effects. After week 8, growth and function affected.

Answer 27

Teratogens

Question 28

Teratogens: * medication * renal damage

Answer 28

ACE inhibitors

Question 29

Teratogens: * medication * absence of digits * multiple anomalies

Answer 29

Alkylating Agents

Question 30

Teratogens: * medication * ototoxicity

Answer 30

Aminoglycosides **A mean guy** hit the baby in the **ear**.

Question 31

Teratogens: * medication * neural tube defects, cardiac defects, cleft palate, skeletal abnormalities (eg. phalanx/nail hypoplasia, facial dysmorphism) * high-dose folate supplementation recommended

Answer 31

Antiepileptic Drugs * Valproate * Carbamazepine * Phenytoin * Phenobarbital

Question 32

Teratogens: * medication * vaginal clear cell adenocarcinoma, congenital * Müllerian anomalies

Answer 32

Diethylstilbestrol

Question 33

Teratogens: * medication * neural tube defects

Answer 33

Folate Antagonists * Trimethoprim * Methotrexate * Antiepileptic Drugs

Question 34

Teratogens: * medication * multiple severe birth defects * contraception mandatory

Answer 34

Isotretinoin

Question 35

Teratogens: * medication * Ebstein anomaly (apical displacement of tricuspid valve)

Answer 35

Lithium

Question 36

Teratogens: * medication * aplasia cutis congenita

Answer 36

Methimazole

Question 37

Teratogens: * medication * discolored teeth * inhibited bone growth

Answer 37

Tetracyclines **Teeth**racyclines

Question 38

Teratogens: * medication * limb defects (phocomelia, micromelia—“flipper” limbs)

Answer 38

Thalidomide Tha-**limb**-domide

Question 39

Teratogens: * medication * bone deformities * fetal hemorrhage * abortion * ophthalmologic abnormalities

Answer 39

Warfarin Do not wage warfare on the baby; keep it **hep**py with **hep**arin (does not cross placenta).

Question 40

Teratogens: * substance abuse * common cause of birth defects and intellectual disability * fetal _____ syndrome

Answer 40

Alcohol

Question 41

Teratogens: * substance abuse * low birth weight * preterm birth * IUGR * placental abruption * vasoconstriction

Answer 41

Cocaine

Question 42

Teratogens: * substance abuse * low birth weight (leading cause in developed countries) * preterm labor * placental problems * IUGR, SIDS, ADHD * vasoconstriction * impaired O₂ delivery

Answer 42

Smoking * Nicotine → vasoconstriction * CO → impaired O₂ delivery

Question 43

Teratogens: * congenital goiter * hypothyroidism (cretinism)

Answer 43

Iodine (lack or excess)

Question 44

Teratogens: * Caudal Regression Syndrome * anal atresia to sirenomelia * congenital heart defects (eg. VSD, transposition of the great vessels) * neural tube defects, macrosomia, neonatal hypoglycemia, polycythemia

Answer 44

Maternal Diabetes

Question 45

Teratogens: * neurotoxicity * highest in swordfish, shark, tilefish, and king mackerel

Answer 45

Methylmercury

Question 46

Teratogens: * spontaneous abortions * birth defects (cleft palate, cardiac)

Answer 46

Vitamin A Excess

Question 47

Teratogens: * microcephaly * intellectual disability * minimized by lead shielding

Answer 47

X-rays

Question 48

Teratogens: * leading cause of intellectual disability in the US * ↑ incidence of congenital abnormalities, including pre- and postnatal developmental retardation, microcephaly, facial abnormalities (eg. smooth philtrum, thin vermillion border [upper lip], small palpebral fissures), limb dislocation, and heart defects * heart-lung fistulas and holoprosencephaly in most severe form * mechanism is failure of cell migration

Answer 48

Fetal Alcohol Syndrome

Question 49

Teratogens: * complex disorder involving CNS, ANS, and GI systems * secondary to maternal opiate use/abuse * risk factors for maternal substance abuse during pregnancy include poor mental health, poor prenatal care, low SES, lack of family support, and HCV * universal screening for substance abuse is recommended in all pregnant patients * newborns may present with uncoordinated sucking reflexes, irritability, high-pitched crying, tremors, tachypnea, sneezing, diarrhea, and possibly seizures

Answer 49

Neonatal Abstinence Syndrome

Question 50

Twinning

Answer 50

* Dizygotic (“fraternal”) twins arise from 2 eggs that are separately fertilized by 2 different sperm (always 2 zygotes) and will have 2 separate amniotic sacs and 2 separate placentas (chorions). * Monozygotic (“identical”) twins arise from 1 fertilized egg (1 egg + 1 sperm) that splits in early pregnancy. * The timing of cleavage determines chorionicity (number of chorions) and amnionicity (number of amnions) (**SCAB**): * 0–4 days: **S**eparate chorion and amnion * 4–8 days: shared **C**horion * 8–12 days: shared **A**mnion * 13+ days: shared **B**ody (conjoined)

Question 51

Placenta

Answer 51

1º site of nutrient and gas exchange between mother and fetus

Question 52

Placenta * fetal component * inner layer of chorionic villi

Answer 52

Cytotrophoblast **C**ytotrophoblast makes **c**ells

Question 53

Placenta * fetal component * outer layer of chorionic villi * synthesizes and secretes hormones, eg. hCG (structurally similar to LH; stimulates corpus luteum to secrete progesterone during first trimester) * lacks MHC-I expression → ↓chance of attack by maternal immune system

Answer 53

Syncytiotrophoblast **Syn**cytiotrophoblast **syn**thesizes hormones

Question 54

Placenta: * maternal component * derived from endometrium * maternal blood in lacunae

Answer 54

Decidua Basalis

Question 55

Umbilical Cord

Answer 55

* _Umbilical Arteries_ (2) * return deoxygenated blood from fetal internal iliac arteries to placenta * _Umbilical Vein_ (1) * supplies oxygenated blood from placenta to fetus * drains into IVC via liver or via ductus venosus * Single umbilical artery (2-vessel cord) is associated with congenital and chromosomal anomalies. * Umbilical arteries and vein are derived from allantois.

Question 56

Urachus

Answer 56

* In the 3rd week the yolk sac forms the allantois, which extends into urogenital sinus. * Allantois becomes the urachus, a duct between fetal bladder and umbilicus. * Failure of urachus to involute can lead to anomalies that may increase risk of infection and/or malignancy (eg. adenocarcinoma) if not treated. * Obliterated urachus is represented by the median umbilical ligament after birth, which is covered by median umbilical fold of the peritoneum.

Question 57

Urachus: total failure of urachus to obliterate → urine discharge from umbilicus

Answer 57

Patent Urachus

Question 58

Urachus: * partial failure of urachus to obliterate * fluid-filled cavity lined with uroepithelium, between umbilicus and bladder * cyst can become infected and present as painful mass below umbilicus

Answer 58

Urachal Cyst

Question 59

Urachus: slight failure of urachus to obliterate → outpouching of bladder

Answer 59

Vesicourachal Diverticulum

Question 60

Vitelline Duct

Answer 60

* connects yolk sac to midgut lumen * 7th week—obliteration of vitelline duct (omphalomesenteric duct)

Question 61

Vitelline Duct: vitelline duct fails to close → meconium discharge from umbilicus

Answer 61

Vitelline Fistula

Question 62

Vitelline Duct: * partial closure of vitelline duct, with patent portion attached to ileum (true diverticulum) * may have heterotopic gastric and/or pancreatic tissue → melena, hematochezia, abdominal pain

Answer 62

Meckel Diverticulum

Question 63

Aortic Arch Derivatives

Answer 63

Develop into arterial system.

Question 64

Aortic Arch Derivatives: part of maxillary artery (branch of external carotid)

Answer 64

1st **1**st arch is **max**imal

Question 65

Aortic Arch Derivatives: * stapedial artery * hyoid artery

Answer 65

2nd **s**econd = **s**tapedial

Question 66

Aortic Arch Derivatives: * common carotid artery * proximal part of internal Carotid artery

Answer 66

3rd **C**arotid = **C** is the **3**rd letter of alphabet

Question 67

Aortic Arch Derivatives: * left—aortic arch * right—proximal part of right subclavian artery

Answer 67

4th **4**th arch (**4** limbs) = systemic

Question 68

Aortic Arch Derivatives: * proximal part of pulmonary arteries * ductus arteriosus

Answer 68

6th

Question 69

Branchial Apparatus

Answer 69

* Composed of branchial clefts, arches, and pouches. * _Branchial Clefts_ * _​_derived from ectoderm * also called branchial grooves * _Branchial Arches_ * derived from mesoderm (muscles, arteries) and neural crest (bones, cartilage) * _Branchial Pouches_ * derived from endoderm * **CAP** covers outside to inside: * **C**lefts = ectoderm * **A**rches = mesoderm + neural crest * **P**ouches = endoderm

Question 70

Branchial Cleft Derivatives: develops into external auditory meatus

Answer 70

1st cleft

Question 71

Branchial Cleft Derivatives: form temporary cervical sinuses, which are obliterated by proliferation of 2nd arch mesenchyme

Answer 71

2nd through 4th clefts

Question 72

Branchial Cleft Derivatives: branchial cleft cyst within lateral neck, anterior to sternocleidomastoid muscle

Answer 72

Persistent Cervical Sinus

Question 73

Branchial Arch Derivatives: * Cartilage: * maxillary process → maxilla, zygomatic bone * mandibular process → Meckel cartilage, → mandible * malleus and incus * sphenomandibular ligament * Muscles: * muscles of mastication (temporalis, masseter, lateral and medial pterygoids) * mylohyoid * anterior belly of digastric * tensor tympani * anterior 2⁄3 of tongue * tensor veli palatini * Nerves: * CN V₃—chew * Pierre Robin Sequence * micrognathia, glossoptosis, cleft palate, airway obstruction * Treacher Collins Syndrome * neural crest dysfunction → mandibular hypoplasia, facial abnormalities

Answer 73

1st Branchial Arch When at the restaurant of the golden **arches**, children tend to first **chew** (1), then **smile** (2), then **swallow styl**ishly (3) or **simply swallow** (4), and then **speak** (6).

Question 74

Branchial Arch Derivatives: * Cartilage: * Reichert Cartilage: * stapes * styloid process * lesser horn of hyoid * stylohyoid ligament * Muscles: * muscles of facial expression * stapedius * stylohyoid * platysma * posterior belly of digastric * Nerves: * CN VII—facial expression, smile * Pierre Robin Sequence * micrognathia, glossoptosis, cleft palate, airway obstruction * Treacher Collins Syndrome * neural crest dysfunction → mandibular hypoplasia, facial abnormalities

Answer 74

2nd Branchial Arch When at the restaurant of the golden **arches**, children tend to first **chew** (1), then **smile** (2), then **swallow styl**ishly (3) or **simply swallow** (4), and then **speak** (6).

Question 75

Branchial Arch Derivatives: * Cartilage: * greater horn of hyoid * Muscles: * stylopharyngeus (innervated by glossopharyngeal nerve) * Nerves: * CN IX—stylopharyngeus, swallow

Answer 75

3rd Branchial Arch When at the restaurant of the golden **arches**, children tend to first **chew** (1), then **smile** (2), then **swallow styl**ishly (3) or **simply swallow** (4), and then **speak** (6).

Question 76

Branchial Arch Derivatives: * Cartilage: * arytenoids * cricoid * corniculate * cuneiform * thyroid * Muscles: * most pharyngeal constrictors * cricothyroid * levator veli palatini all intrinsic muscles of larynx except cricothyroid * Nerves: * CN X—superior laryngeal branch, swallow * 6th arch: CN X—recurrent/inferior laryngeal branch, speak

Answer 76

4th–6th Branchial Arches * 4th Arch * most pharyngeal constrictors, cricothyroid, and levator veli palatini * CN X—superior laryngeal branch, swallow * 6th Arch * all intrinsic muscles of larynx except cricothyroid * CN X (recurrent/inferior laryngeal branch) speak * Arches 3 and 4 form posterior 1⁄3 of tongue. * Arch 5 makes no major developmental contributions. Sing and **ACCCT**: * **A**rytenoids * **C**ricoid * **C**orniculate * **C**uneiform * **T**hyroid When at the restaurant of the golden **arches**, children tend to first **chew** (1), then **smile** (2), then **swallow styl**ishly (3) or **simply swallow** (4), and then **speak** (6).

Question 77

Branchial Pouch Derivatives: * middle ear cavity * eustachian tube * mastoid air cells * contributes to endoderm-lined structures of ear

Answer 77

1st Branchial Pouch **ears**, **tonsils**, **bottom**-**to**-**top**: * 1 (**ears**) * 2 (**tonsils**) * 3 dorsal (**bottom** = inferior parathyroids) * 3 ventral (**to** = thymus) * 4 (**top** = superior parathyroids)

Question 78

Branchial Pouch Derivatives: epithelial lining of palatine tonsil

Answer 78

2nd Branchial Pouch **ears**, **tonsils**, **bottom**-**to**-**top**: * 1 (**ears**) * 2 (**tonsils**) * 3 dorsal (**bottom** = inferior parathyroids) * 3 ventral (**to** = thymus) * 4 (**top** = superior parathyroids)

Question 79

Branchial Pouch Derivatives: * dorsal wings → inferio parathyroids * ventral wings → thymus * contributes to 3 structures (thymus, left and right inferior parathyroids) * end up below 4th-pouch structures

Answer 79

3rd Branchial Pouch **ears**, **tonsils**, **bottom**-**to**-**top**: * 1 (**ears**) * 2 (**tonsils**) * 3 dorsal (**bottom** = inferior parathyroids) * 3 ventral (**to** = thymus) * 4 (**top** = superior parathyroids)

Question 80

Branchial Pouch Derivatives: * dorsal wings → superior parathyroids * ventral wings → ultimobranchial body → parafollicular cells of thyroid

Answer 80

4th Branchial Pouch **ears**, **tonsils**, **bottom**-**to**-**top**: * 1 (**ears**) * 2 (**tonsils**) * 3 dorsal **(bottom** = inferior parathyroids) * 3 ventral (**to** = thymus) * 4 (**top** = superior parathyroids)

Question 81

Branchial Pouch: * chromosome 22q11 deletion * aberrant development of 3rd and 4th pouches → T-cell deficiency (thymic aplasia) and hypocalcemia (failure of parathyroid development) * associated with cardiac defects (conotruncal anomalies)

Answer 81

DiGeorge Syndrome

Question 82

Cleft Lip and Palate

Answer 82

* Cleft Lip * failure of fusion of the maxillary an merged medial nasal processes (formation of 1° palate) * Cleft Palate * failure of fusion of the two lateral palatine shelves or failure of fusion of lateral palatine shelves with the nasal septum and/or median palatine shelf (formation of 2° palate) * Cleft lip and cleft palate have distinct, multifactorial etiologies, but often occur together.

Question 83

Genital Embryology: Female

Answer 83

* default development * mesonephric duct degenerates and paramesonephric duct develops

Question 84

Genital Embryology: Male

Answer 84

* SRY gene on Y chromosome—produces testis-determining factor → testes development * Sertoli cells secrete Müllerian inhibitory factor (MIF) that suppresses development of paramesonephric ducts. * Leydig cells secrete androgens that stimulate development of mesonephric ducts.

Question 85

Genital Embryology: Paramesonephric (Müllerian) Duct

Answer 85

* develops into female internal structures—fallopian tubes, uterus, upper portion of vagina (lower portion from urogenital sinus) * male remnant is appendix testis

Question 86

Genital Embryology: may present as 1° amenorrhea (due to a lack of uterine development) in females with fully developed 2° sexual characteristics (functional ovaries)

Answer 86

Müllerian Agenesis (Mayer-Rokitansky-Küster-Hauser syndrome)

Question 87

Genital Embryology: Mesonephric (Wolffian) Duct

Answer 87

* develops into male internal structures (except prostate) * **SEED**: * **S**eminal vesicles * **E**pididymis * **E**jaculatory duct * **D**uctus deferens * female remnant is Gartner duct

Question 88

Sexual Differentiation

Answer 88

① no Sertoli cells or lack of Müllerian inhibitory factor → develop both male and female internal genitalia and male external genitalia ② 5α-reductase deficiency—inability to convert testosterone into DHT → male internal genitalia, ambiguous external genitalia until puberty (when ↑ testosterone levels cause masculinization) In the testes: * **L**eydig cells **L**eads to male (internal and external) sexual differentiation. * **S**ertoli cells **S**huts down female (internal) sexual differentiation.

Question 89

Uterine (Müllerian Duct) Anomalies: * common anomaly * incomplete resorption of septum * ↓ fertility and early miscarriage/pregnancy loss * treated with septoplasty

Answer 89

Septate Uterus

Question 90

Uterine (Müllerian Duct) Anomalies: * incomplete fusion of Müllerian ducts * ↑ risk of complicated pregnancy, early pregnancy loss, malpresentation, prematurity

Answer 90

Bicornuate Uterus

Question 91

Uterine (Müllerian Duct) Anomalies: * complete failure of fusion → double uterus, cervix, vagina * pregnancy possible

Answer 91

Uterus Didelphys

Question 92

Male/Female Genital Homologs

Answer 92

Question 93

Congenital Penile Abnormalities: * abnormal opening of penile urethra on ventral surface of penis due to failure of urethral folds to fuse * more common than epispadias * associated with inguinal hernia and cryptorchidism

Answer 93

Hypospadias

Question 94

Congenital Penile Abnormalities: * abnormal opening of penile urethra on dorsal surface of penis due to faulty positioning of genital tubercle * associated with exstrophy of the bladder is

Answer 94

Epispadias When you have **E**pispadias, you hit your **E**ye when you p**EE**.

Question 95

Descent of Testes and Ovaries: * band of fibrous tissue * Male Remnant: * anchors testes within scrotum * Female Remnant: * ovarian ligament + round ligament of uterus

Answer 95

Gubernaculum

Question 96

Descent of Testes and Ovaries: * evagination of peritoneum * Male Remnant: * forms tunica vaginalis * Female Remnant: * obliterated

Answer 96

Processus Vaginalis

Question 97

Gonadal Venous Drainage

Answer 97

* right ovary/testis → right gonadal vein → IVC * left ovary/testis → left gonadal vein → left renal vein → IVC * “**L**eft gonadal vein takes the **L**ongest way.” * Because the left spermatic vein enters the left renal vein at a 90° angle, flow is less laminar on left than on right → left venous pressure \> right venous pressure → varicocele more common on the left.

Question 98

Gonadal Lymphatic Drainage

Answer 98

* ovaries/testes → para-aortic lymph nodes * body of uterus/superior bladder → external iliac nodes * prostate/cervix/corpus cavernosum/proximal vagina → internal iliac nodes * distal vagina/vulva/scrotum/distal anus → superficial inguinal nodes * glans penis → deep inguinal nodes

Question 99

Female Reproductive Anatomy

Answer 99

Question 100

Female Reproductive Anatomy: * connects ovaries to lateral pelvic wall * contains ovarian vessels * also called suspensory ligament of the ovary * ligate vessels during oophorectomy to avoid bleeding * ureter courses retroperitoneally, close to gonadal vessels → at risk of injury during ligation of ovarian vessels

Answer 100

Infundibulopelvic Ligament

Question 101

Female Reproductive Anatomy: * connects cervix to side wall of pelvis * contains uterine vessels * ureter at risk of injury during ligation of uterine vessels in hysterectomy

Answer 101

Cardinal ligament

Question 102

Female Reproductive Anatomy: * connects uterine horn to labia majora * derivative of gubernaculum * travels through round inguinal canal * above the artery of Sampson

Answer 102

Round Ligament of the Uterus

Question 103

Female Reproductive Anatomy: * connects uterus, fallopian tubes, and ovaries to pelvic side wall * contains ovaries, fallopian tubes, and round ligaments of uterus * fold of peritoneum that comprises the mesosalpinx, mesometrium, and mesovarium

Answer 103

Broad Ligament

Question 104

Female Reproductive Anatomy: * medial pole of ovary to uterine horn * derivative of gubernaculum

Answer 104

Ovarian Ligament Ovarian Ligament **L**atches to **L**ateral uterus.

Question 105

Female Reproductive Epithelial Histology: Vagina

Answer 105

nonkeratinized stratified squamous epithelium

Question 106

Female Reproductive Epithelial Histology: Ectocervix

Answer 106

nonkeratinized stratified squamous epithelium

Question 107

Female Reproductive Epithelial Histology: Transformation Zone

Answer 107

squamocolumnar junction * most common area for cervical cancer

Question 108

Female Reproductive Epithelial Histology: Endocervix

Answer 108

simple columnar epithelium

Question 109

Female Reproductive Epithelial Histology: Uterus

Answer 109

simple columnar epithelium * proliferative phase—long tubular glands * secretory phase—coiled glands

Question 110

Female Reproductive Epithelial Histology: Fallopian Tube

Answer 110

ciliated simple columnar epithelium

Question 111

Female Reproductive Epithelial Histology: outer surface of the ovaries

Answer 111

simple cuboidal epithelium * germinal epithelium covering surface of ovary

Question 112

Male Reproductive Anatomy

Answer 112

Pathway of Sperm during Ejaculation—**SEVEN UP**: * **S**eminiferous tubules * **E**pididymis * **V**as deferens * **E**jaculatory ducts * (**N**othing) * **U**rethra * **P**enis

Question 113

\_\_\_\_\_ occurs almost exclusively in men. Suspect if blood seen at urethral meatus. Urethral catheterization is relatively contraindicated.

Answer 113

Urethral Injury

Question 114

Urethral Injury: * bulbar (spongy) urethra * perineal straddle injury * blood accumulates in scrotum * if Buck fascia is torn, urine escapes into perineal space * blood at urethral meatus and scrotal hematoma

Answer 114

Anterior Urethral Injury

Question 115

Urethral Injury: * membranous urethra * pelvic fracture * urine leaks into retropubic space * blood at urethral meatus and high-riding prostate

Answer 115

Posterior Urethral Injury

Question 116

Autonomic Innervation of Male Sexual Response

Answer 116

**P**oint, **S**queeze, and **S**hoot. * Erection * **P**arasympathetic nervous system (pelvic splanchnic nerves, S2-S4): * NO → ↑ cGMP → smooth muscle relaxation → vasodilation → proerectile * PDE-5 inhibitors (eg. Sildenafil) ↓ cGMP breakdown * Norepinephrine → ↑ [Ca²⁺]_in → smooth muscle contraction → vasoconstriction → antierectile * Emission * **S**ympathetic nervous system (hypogastric nerve, T11-L2) * Ejaculation * visceral and **S**omatic nerves (pudendal nerve)

Question 117

Seminiferous Tubules

Answer 117

Question 118

Seminiferous Tubules: * maintain germ cell pool and produce 1° spermatocytes * line seminiferous tubules * germ cells

Answer 118

Spermatogonia

Question 119

Seminiferous Tubules: * secrete inhibin B → inhibit FSH * secrete androgen-binding protein → maintain local levels of testosterone * produce MIF * tight junctions between adjacent _____ form blood-testis barrier → isolate gametes from autoimmune attack * support and nourish developing spermatozoa * regulate spermatogenesis * temperature sensitive * ↓ sperm production and ↓ inhibin B with ↑ temperature * line seminiferous tubules * non-germ cells * convert testosterone and androstenedione to estrogens via aromatase * homolog of female granulosa cells ↑ temperature seen in varicocele, cryptorchidism

Answer 119

Sertoli Cells **S**ertoli cells **S**upport **S**perm **S**ynthesis and inhibit F**S**H.

Question 120

Seminiferous Tubules: * secrete testosterone in the presence of LH * testosterone production unaffected by temperature * interstitium * endocrine cells * homolog of female theca interna cells

Answer 120

Leydig Cells **L**H stimulates **L**eydig cells.

Question 121

Estrogen

Answer 121

* Sources: * ovary (17β-estradiol) * placenta (estriol) * adipose tissue (estrone via aromatization) * Potency: estradiol \> estrone \> estriol * Function: * development of genitalia and breast * female fat distribution * growth of follicle * endometrial proliferation * ↑ myometrial excitability * upregulation of estrogen, LH, and progesterone receptors * feedback inhibition of FSH and LH, then LH surge * stimulation of prolactin secretion * ↑ transport proteins, SHBG * ↑ HDL * ↓ LDL * Pregnancy: * 50-fold ↑ in estradiol and estrone * 1000-fold ↑ in estriol (indicator of fetal well-being) * Estrogen receptors expressed in cytoplasm; translocate to nucleus when bound by estrogen.

Question 122

Progesterone

Answer 122

* Source: * corpus luteum * placenta * adrenal cortex * testes * Function: * stimulation of endometrial glandular secretions and spiral artery development * maintenance of pregnancy * ↓ myometrial excitability * production of thick cervical mucus, which inhibits sperm entry into uterus * ↑ body temperature * inhibition of gonadotropins (LH, FSH) * uterine smooth muscle relaxation (preventing contractions) * ↓ estrogen receptor expression * prevents endometrial hyperplasia * Fall in progesterone after delivery disinhibits prolactin → lactation. * ↑ progesterone is indicative of ovulation. * **Prog**esterone is **pro**-**g**estation. * **Prol**actin is **pro**-**l**actation.

Question 123

Oogenesis

Answer 123

* 1° oocytes begin meiosis I during fetal life and complete meiosis I just prior to ovulation. * Meiosis I is arrested in Pr**O**phase I for years until **O**vulation (1° oocytes). * Meiosis II is arrested in **Met**aphase II until fertilization (2° oocytes). “An egg **met** a sperm.” * If fertilization does not occur within 1 day, the 2° oocyte degenerates.

Question 124

Ovulation

Answer 124

* ↑ estrogen, ↑ GnRH receptors on anterior pituitary * Estrogen surge then stimulates LH release → ovulation (rupture of follicle). * ↑ temperature (progesterone induced)

Question 125

\_\_\_\_\_ is the transient mid-cycle ovulatory pain (“middle hurts”); classically associated with peritoneal irritation (eg. follicular swelling/rupture, fallopian tube contraction). Can mimic appendicitis.

Answer 125

Mittelschmerz

Question 126

Menstrual Cycle

Answer 126

* Follicular phase can vary in length. * Luteal phase is 14 days. * ovulation day + 14 days = menstruation * Follicular growth is fastest during 2nd week of the follicular phase. * Estrogen stimulates endometrial proliferation. * Progesterone maintains endometrium to support implantation. * ↓ progesterone → ↓ fertility

Question 127

Abnormal Uterine Bleeding

Answer 127

* Characterized as either heavy menstrual bleeding (AUB/HMB) or intermenstrual bleeding (AUB/IMB). * These are further subcategorized by **PALMCOEIN**: * Structural Causes (**PALM**): * **P**olyp * **A**denomyosis * **L**eiomyoma * **M**alignancy/hyperplasia * Non-Structural Causes (**COEIN**): * **C**oagulopathy * **O**vulatory * **E**ndometrial * **I**atrogenic * **N**ot yet classified * Terms such as dysfunctional uterine bleeding, menorrhagia, oligomenorrhea are no longer recommended.

Question 128

Pregnancy

Answer 128

* Fertilization most commonly occurs in upper end of fallopian tube (the ampulla). * Occurs within 1 day of ovulation. * Implantation within the wall of the uterus occurs 6 days after fertilization. * Syncytiotrophoblasts secrete hCG, which is detectable in blood 1 week after conception and on home test in urine 2 weeks after conception. * _Gestational Age_—calculated from date of last menstrual period * _Embryonic Age_—calculated from date of conception (gestational age minus 2 weeks) * Physiologic adaptations in pregnancy: * ↑ cardiac output (↑ preload, ↓ afterload, ↑ HR → ↑ placental and uterus perfusion) * anemia (↑↑ plasma, ↑ RBCs) * hypercoagulability (to ↓ blood loss at * delivery) * hyperventilation (eliminate fetal CO₂) * Placental hormone secretion generally increases over the course of pregnancy, but hCG peaks at 8–10 weeks.

Question 129

Human Chorionic Gonadotropin

Answer 129

* Source: syncytiotrophoblast of placenta * Function: * Maintains corpus luteum (and thus progesterone) for first 8–10 weeks of pregnancy by acting like LH (otherwise no luteal cell stimulation → abortion). * After 8–10 weeks, placenta synthesizes its own estriol and progesterone and corpus luteum degenerates. * Used to detect pregnancy because it appears early in urine. * Has identical α subunit as LH, FSH, TSH (states of ↑ hCG can cause hyperthyroidism). * β subunit is unique (pregnancy tests detect β subunit). * hCG is ↑ in multiple gestations, hydatidiform moles, choriocarcinomas, and Down syndrome. * hCG is ↓ in ectopic/failing pregnancy, Edwards syndrome, and Patau syndrome.

Question 130

Human Placental Lactogen

Answer 130

* also known as Chorionic Somatomammotropin * Source: syncytiotrophoblast of placenta * Function: * Stimulates insulin production; overall ↑ insulin resistance. * Maternal hypoglycemia from insulin resistance leads to lipolysis, which preserves available glucose and amino acids for the fetus. * Gestational diabetes can occur if maternal pancreatic function cannot overcome the insulin resistance.

Question 131

Apgar Score

Answer 131

* Assessment of newborn vital signs following delivery via a 10-point scale evaluated at 1 minute and 5 minutes. * Apgar score is based on Appearance, Pulse, Grimace, Activity, and Respiration. * Apgar scores \< 7 require further evaluation. * If Apgar score remains low at later time points, there is ↑ risk the child will develop long-term neurologic damage.

Question 132

Infant/Child Development

Answer 132

* Milestone dates are ranges that have been approximated and vary by source. * Children not meeting milestones may need assessment for potential developmental delay.

Question 133

Low Birth Weight

Answer 133

* Defined as \< 2500 g. * Caused by prematurity or intrauterine growth restriction (IUGR). * Associated with ↑ risk of sudden infant death syndrome (SIDS) and with ↑ overall mortality. * Other problems include impaired thermoregulation and immune function, hypoglycemia, polycythemia, and impaired neurocognitive/emotional development. * Complications include infections, respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, and persistent fetal circulation.

Question 134

Lactation

Answer 134

* After parturition and delivery of placenta, rapid ↓ in progesterone disinhibits and initiates lactation. * Suckling is required to maintain milk production and ejection, since ↑ nerve stimulation → ↑ oxytocin and prolactin. * _Prolactin_—induces and maintains lactation and ↓ reproductive function. * _Oxytocin_—assists in milk letdown; also promotes uterine contractions. * Breast milk is the ideal nutrition for infants \< 6 months old. * Contains maternal immunoglobulins (conferring passive immunity; mostly IgA), macrophages, lymphocytes. * Breast milk reduces infant infections and is associated with ↓ risk for child to develop asthma, allergies, diabetes mellitus, and obesity. * Guidelines recommend exclusively breastfed infants get vitamin D and possibly iron supplementation. * Breastfeeding ↓ maternal risk of breast and ovarian cancer and facilitates mother-child bonding.

Question 135

Menopause

Answer 135

* Diagnosed by amenorrhea for 12 months. * ↓ estrogen production due to age-linked decline in number of ovarian follicles. * Average age at onset is 51 years (earlier in smokers). * Usually preceded by 4–5 years of abnormal menstrual cycles. * Source of estrogen (estrone) after menopause becomes peripheral conversion of androgens, ↑ androgens → hirsutism. * ↑↑ FSH is specific for menopause (loss of negative feedback on FSH due to ↓ estrogen). * Hormonal Changes: * ↓ estrogen * ↑↑ FSH * ↑ LH (no surge) * ↑ GnRH * Causes **HAVOCS**: * **H**ot flashes * **A**trophy of the **V**agina * **O**steoporosis * **C**oronary artery disease * **S**leep disturbances * Menopause before age 40 suggests 1° ovarian insufficiency (premature ovarian failure).

Question 136

Androgens

Answer 136

* Testosterone, Dihydrotestosterone (DHT), and Androstenedione * Sources: * DH**T** and **T**estosterone (**T**estis) * **A**n**D**rostenedione (**AD**renal) * Potency: DHT \> testosterone \> androstenedione * Function: * Testosterone: * differentiation of epididymis, vas deferens, and seminal vesicles (internal genitalia, except prostate). * growth spurt: penis, seminal vesicles, sperm, muscle, RBCs * deepening of voice * closing of epiphyseal plates (via estroge converted from testosterone) * libido * DHT: * Early—differentiation of penis, scrotum, prostate * Late—prostate growth, balding, sebaceous gland activity * Testosterone is converted to DHT by 5α-reductase, which is inhibited by Finasteride. * In the male, androgens are converted to estrogen by cytochrome P-450 aromatase (primarily in adipose tissue and testis). * Aromatase is the key enzyme in conversion of androgens to estrogen. * Exogenous testosterone → inhibition of hypothalamic–pituitary–gonadal axis → ↓ intratesticular testosterone → ↓ testicular size → azoospermia.

Question 137

Spermatogenesis

Answer 137

* Spermatogenesis begins at puberty with spermatogonia. * Full development takes 2 months. * Occurs in seminiferous tubules. * Produces spermatids that undergo spermiogenesis (loss of cytoplasmic contents, gain of acrosomal cap) to form mature spermatozoon. * “**Go**nium” is **go**ing to be a sperm. * “**Zoo**n” is “**zoo**ming” to the egg.

Question 138

Tanner Stages of Sexual Development

Answer 138

Tanner stage is assigned independently to genitalia, pubic hair, and breast (eg. a person can have Tanner stage 2 genitalia, Tanner stage 3 pubic hair).

Question 139

Aneuploidy most commonly due to \_\_\_\_\_.

Answer 139

Meiotic Nondisjunction

Question 140

Sex Chromosome Disorders: * Male, 47, XXY * testicular atrophy, eunuchoid body shape, tall, long extremities, gynecomastia, female hair distribution * may present with developmental delay * presence of inactivated X chromosome (Barr body) * common cause of hypogonadism seen in infertility work-up * dysgenesis of seminiferous tubules → ↓ inhibin B → ↑ FSH * abnormal Leydig cell function → ↓ testosterone → ↑ LH → ↑ estrogen

Answer 140

Klinefelter Syndrome

Question 141

Sex Chromosome Disorders: * Female, 45, XO * short stature (if untreated; preventable with growth hormone therapy), ovarian dysgenesis (streak ovary), shield chest, bicuspid aortic valve, coarctation (femoral \< brachial pulse), lymphatic defects (result in webbed neck or cystic hygroma, lymphedema in hands and feet), horseshoe kidney * most common cause of 1° amenorrhea * no Barr body * menopause before menarche * ↓ estrogen leads to ↑LH, FSH * sometimes due to mitotic error → mosaicism (eg. 45, XO/46, XX) * pregnancy is possible in some cases (IVF, exogenous estradiol-17β and progesterone)

Answer 141

Turner Syndrome

Question 142

Sex Chromosome Disorders: * 47, XYY * phenotypically normal (usually undiagnosed), very tall * normal fertility * may be associated with severe acne, learning disability, and autism spectrum disorders

Answer 142

Double Y Males

Question 143

Sex Chromosome Disorders: * 46, XX \> 46, XY * both ovarian and testicular tissue present (ovotestis) * ambiguous genitalia * previously called true hermaphroditism

Answer 143

Ovotesticular Disorder of Sex Development

Question 144

Diagnosing Disorders of Sex Hormones: * ↑ Testosterone * ↑ LH

Answer 144

Defective Androgen Receptor

Question 145

Diagnosing Disorders of Sex Hormones: * ↑ Testosterone * ↓ LH

Answer 145

Testosterone-Secreting Tumor * exogenous steroids

Question 146

Diagnosing Disorders of Sex Hormones: * ↓ Testosterone * ↑ LH

Answer 146

1° Hypergonadotropic Hypogonadism

Question 147

Diagnosing Disorders of Sex Hormones: * ↓ Testosterone * ↓ LH

Answer 147

2° Hypogonadotropic Hypogonadism

Question 148

Other Disorders of Sex Development

Answer 148

* Disagreement between the phenotypic sex (external genitalia, influenced by hormonal levels) and the gonadal sex (testes vs. ovaries, corresponds with Y chromosome). * Includes the terms pseudohermaphrodite, hermaphrodite, and intersex.

Question 149

Other Disorders of Sex Development: * ovaries present, but external genitalia are virilized or ambiguous * due to excessive and inappropriate exposure to androgenic steroids during early gestation (eg. congenital adrenal hyperplasia or exogenous administration of androgens during pregnancy)

Answer 149

46, XX DSD

Question 150

Other Disorders of Sex Development: * testes present, but external genitalia are female or ambiguous * most common form is androgen insensitivity syndrome (testicular feminization)

Answer 150

46, XY DSD

Question 151

Disorders by Physical Characteristics: * ⊕ Uterus * ⊝ Breasts

Answer 151

Hypergonadotropic Hypogonadism * Turner syndrome * genetic mosaicism * pure gonadal dysgenesis Hypogonadotropic Hypogonadism * CNS lesions * Kallmann syndrome

Question 152

Disorders by Physical Characteristics: * ⊝ Uterus * ⊕ Breasts

Answer 152

Uterovaginal Agenesis * genotypic female Androgen Insensitivity * genotypic male

Question 153

Disorders by Physical Characteristics: * ⊝ Uterus * ⊝ Breasts

Answer 153

male genotype with insufficient production of testosterone

Question 154

Reproductive Pathology: * inability to synthesize estrogens from androgens * masculinization of female (46, XX DSD) infants (ambiguous genitalia) * ↑ serum testosterone and androstenedione * can present with maternal virilization during pregnancy (fetal androgens cross the placenta)

Answer 154

Placental Aromatase Deficiency

Question 155

Reproductive Pathology: * defect in androgen receptor resulting in normal-appearing female (46, XY DSD) * female external genitalia with scant axillary and pubic hair * rudimentary vagina * uterus and fallopian tubes absent * patients develop normal functioning testes (often found in labia majora; surgically removed to prevent malignancy) * ↑ testosterone, estrogen, and LH (vs. sex chromosome disorders)

Answer 155

Androgen Insensitivity Syndrome

Question 156

Reproductive Pathology: * autosomal recessive * sex limited to genetic males (46, XY DSD) * inability to convert testosterone to DHT * ambiguous genitalia until puberty, when ↑ testosterone causes masculinization/↑ growth of external genitalia * testosterone/estrogen levels are normal * LH is normal or ↑ * internal genitalia are normal

Answer 156

5α-Reductase Deficiency

Question 157

Reproductive Pathology: * failure to complete puberty * a form of hypogonadotropic hypogonadism * defective migration of GnRH-releasing neurons and subsequent failure of GnRH-releasing olfactory bulbs to develop → ↓ synthesis of GnRH in the hypothalamus * hyposmia/anosmia * ↓ GnRH, FSH, LH, and testosterone * infertility (low sperm count in males; amenorrhea in females)

Answer 157

Kallmann Syndrome

Question 158

Hydatidiform Mole

Answer 158

* cystic swelling of chorionic villi and proliferation of chorionic epithelium (only trophoblast) * presents with vaginal bleeding, uterine enlargement more than expected, pelvic pressure/pain * associated with hCG-mediated sequelae: early preeclampsia (before 20 weeks), theca-lutein cysts, hyperemesis gravidarum, and hyperthyroidism * Treatment: * dilation and curettage * Methotrexate * monitor β-hCG

Question 159

Hydatidiform Mole: * Karyotype: 46, XX; 46, XY * Components: * most commonly enucleated egg + single sperm (subsequently duplicates paternal DNA) * Fetal Parts: No * Uterine Size: ↑ * hCG: ↑↑↑↑ * Imaging: * “honeycombed” uterus or “clusters of grapes” * “snowstorm” on ultrasound * Risk of Gestational Trophoblastic Neoplasia: 15–20% * Risk of Choriocarcinoma: 2%

Answer 159

Complete Mole

Question 160

Hydatidiform Mole: * Karyotype: 69, XXX; 69, XXY; 69, XYY * Components: 2 sperm + 1 egg * Fetal Parts: Yes * Uterine Size: — * hCG: ↑ * Imaging: fetal parts * Risk of Gestational Trophoblastic Neoplasia: \< 5% * Risk of Choriocarcinoma: rare

Answer 160

Partial Mole **part**ial = fetal **part**s

Question 161

Reproductive Pathology: * rare * can develop during or after pregnancy in mother or baby * malignancy of trophoblastic tissue (cytotrophoblasts, syncytiotrophoblasts) * no chorionic villi present * ↑ frequency of bilateral/multiple theca-lutein cysts * presents with abnormal ↑ β-hCG, shortness of breath, and hemoptysis * hematogenous spread to lungs → “cannonball” metastases

Answer 161

Choriocarcinoma

Question 162

Pregnancy Complications: * premature separation (partial or complete) of placenta from uterine wall before delivery of infant * Risk Factors: * trauma (eg. motor vehicle accident) * smoking * hypertension * preeclampsia * cocaine abuse * Presentation: * abrupt * painful bleeding (concealed or apparent) in third trimester * possible DIC * maternal shock * fetal distress * life threatening for mother and fetus

Answer 162

Abruptio Placentae

Question 163

Pregnancy Complications: * defective decidual layer → abnormal attachment and separation after delivery * Risk Factors: * prior C-section or uterine surgery involving myometrium * inflammation * placenta previa * advanced maternal age * multiparity * Three types distinguishable by the depth of penetration: * _Placenta Accreta_ * placenta attaches to myometrium without penetrating it * most common type * _Placenta Increta_ * placenta penetrates into myometrium * _Placenta Percreta_ * placenta penetrates (“perforates”) through myometrium and into uterine serosa (invades entire uterine wall) * can result in placental attachment to rectum or bladder (can result in hematuria) * Presentation: * often detected on ultrasound prior to delivery * no separation of placenta after delivery → postpartum bleeding (can cause Sheehan syndrome)

Answer 163

Morbidly Adherent Placenta

Question 164

Pregnancy Complications: * attachment of placenta to lower uterine segment over (or \< 2 cm from) internal cervical os * Risk Factors: * multiparity * prior C-section * associated with painless third-trimester bleeding

Answer 164

Placenta Previa A “**previ**ew” of the placenta is visible through cervix.

Question 165

Pregnancy Complications: * fetal vessels run over, or in close proximity to, cervical os * may result in vessel rupture, exsanguination, and fetal death * presents with triad of membrane rupture, painless vaginal bleeding, and fetal bradycardia (\< 110 beats/min) * emergency C-section usually indicated * frequently associated with velamentous umbilical cord insertion (cord inserts in chorioamniotic membrane rather than placenta → fetal vessels travel to placenta unprotected by Wharton jelly)

Answer 165

Vasa Previa

Question 166

Pregnancy Complications: * Due to **4 T**’s: * **T**one (uterine atony; most common) * **T**rauma (lacerations, incisions, uterine rupture) * **T**hrombin (coagulopathy) * **T**issue (retained products of conception)

Answer 166

Postpartum Hemorrhage

Question 167

Pregnancy Complications: * implantation of fertilized ovum in a site other than the uterus * most often in ampulla of fallopian tube * suspect with history of amenorrhea, lower-than-expected rise in hCG based on dates, and sudden lower abdominal pain * confirm with ultrasound * often clinically mistaken for appendicitis * pain +/− bleeding * Risk Factors: * prior \_\_\_\_\_ * history of infertility * salpingitis (PID) * ruptured appendix * prior tubal surgery * smoking * advanced maternal age

Answer 167

Ectopic Pregnancy

Question 168

Amniotic Fluid Abnormalities: * too much amniotic fluid * often idiopathic, but associated with fetal malformations (eg. esophageal/duodenal atresia, anencephaly; both result in inability to swallow amniotic fluid), maternal diabetes, fetal anemia, and multiple gestations

Answer 168

Polyhydramnios

Question 169

Amniotic Fluid Abnormalities: * too little amniotic fluid * associated with placental insufficiency, bilateral renal agenesis, posterior urethral valves (in males) and resultant inability to excrete urine * any profound _____ can cause Potter sequence

Answer 169

Oligohydramnios

Question 170

Hypertension in Pregnancy: * BP \> 140/90 mmHg after 20th week of gestation * no pre-existing hypertension * no proteinuria or end-organ damage * Treatment: * antihypertensives * deliver at 37–39 weeks

Answer 170

Gestational Hypertension **H**ypertensive **M**oms **L**ove **N**ifedipine. * **H**ydralazine * α-**M**ethyldopa * **L**abetalol * **N**ifedipine

Question 171

Hypertension in Pregnancy: * new-onset hypertension with either proteinuria or end-organ dysfunction after 20th week of gestation (\< 20 weeks suggests molar pregnancy) * caused by abnormal placental spiral arteries → endothelial dysfunction, vasoconstriction, ischemia * incidence ↑ in patients with pre-existing hypertension, diabetes, chronic renal disease, and autoimmune disorders (eg. antiphospholipid antibody syndrome) * Complications: * placental abruption * coagulopathy * renal failure * pulmonary edema * uteroplacental insufficiency * may lead to eclampsia (+ seizures) and/or HELLP syndrome * Treatment: * antihypertensives * IV magnesium sulfate (to prevent seizure) * definitive is delivery of fetus

Answer 171

Preeclampsia

Question 172

Hypertension in Pregnancy: * preeclampsia + maternal seizures * maternal death due to stroke, intracranial hemorrhage, or ARDS * Treatment: * IV magnesium sulfate * antihypertensives * immediate delivery

Answer 172

Eclampsia

Question 173

Hypertension in Pregnancy: * hemolysis, elevated liver enzymes, and low platelets * a manifestation of severe preeclampsia * blood smear shows schistocytes * can lead to DIC and hepatic subcapsular hematomas → rupture → severe hypotension * Treatment: immediate delivery

Answer 173

HELLP syndrome * **H**emolysis * **E**levated **L**iver Enzymes * **L**ow **P**latelets

Question 174

Gynecologic Tumor Epidemiology

Answer 174

* Incidence (US): * endometrial \> ovarian \> cervical * cervical cancer is more common worldwide due to lack of screening or HPV vaccination * Prognosis: * **C**ervical—best prognosis, diagnosed \< 45 years old * **E**ndometrial—middle-aged, about 55 years old * **O**varian—worst prognosis, \> 65 years * **CEO**s often go from **best to worst** as they get **older**.

Question 175

Vulvar Pathology: * non-neoplastic * due to blockage of Bartholin gland duct causing accumulation of gland fluid * may lead to abscess 2° to obstruction and inflammation * usually in reproductive-age females * associated with *N. gonorrhoeae* infections

Answer 175

Bartholin Cyst and Abscess

Question 176

Vulvar Pathology: * non-neoplastic * thinning of epidermis with fibrosis/sclerosis of dermis * presents with porcelain-white plaques with a red or violet border * skin fragility with erosions can be observed * most common in postmenopausal women * benign, but slightly increased risk for SCC

Answer 176

Lichen Sclerosus

Question 177

Vulvar Pathology: * non-neoplastic * hyperplasia of vulvar squamous epithelium * presents with leathery, thick vulvar skin with enhanced skin markings due to chronic rubbing or scratching * benign, no risk of SCC

Answer 177

Lichen Simplex Chronicus

Question 178

Vulvar Pathology: * neoplastic * carcinoma from squamous epithelial lining of vulva * rare * presents with leukoplakia * biopsy often required to distinguish carcinoma from other causes * HPV-Related * associated with high-risk HPV types 16, 18 * Risk Factors: * multiple partners * early coitarche * usually in reproductive-age females * Non-HPV * usually from long-standing lichen sclerosus * females \> 70 years old

Answer 178

Vulvar Carcinoma

Question 179

Vulvar Pathology: * neoplastic * intraepithelial adenocarcinoma * carcinoma in situ * low risk of underlying carcinoma * presents with pruritus, erythema, crusting, and ulcers

Answer 179

Extramammary Paget Disease

Question 180

Vaginal Tumors: * usually 2° to cervical SCC * 1° vaginal carcinoma is rare

Answer 180

Vaginal Squamous Cell Carcinoma

Question 181

Vaginal Tumors: affects women who had exposure to DES in utero

Answer 181

Clear Cell Adenocarcinoma

Question 182

Vaginal Tumors: * embryonal rhabdomyosarcoma variant * affects girls \< 4 years old * spindle-shaped cells * desmin ⊕ * presents with clear, grape-like, polypoid mass emerging from vagina

Answer 182

Sarcoma Botryoides

Question 183

Cervical Pathology: * disordered epithelial growth * begins at basal layer of squamocolumnar junction (transformation zone) and extends outward * classified as CIN 1, CIN 2, or CIN 3 (severe, irreversible dysplasia), depending on extent of dysplasia * associated with HPV-16 and HPV-18, which produce both the E6 gene product (inhibits p53) and E7 gene product (inhibits pRb) * koilocytes are pathognomonic of HPV infection * may progress slowly to invasive carcinoma if left untreated * typically asymptomatic (detected with Pap smear) or presents as abnormal vaginal bleeding (often postcoital) * Risk Factors: * multiple sexual partners (#1) * smoking * early coitarche * DES exposure * immunocompromise (eg. HIV, transplant)

Answer 183

Dysplasia and Carcinoma in situ

Question 184

Cervical Pathology: * often squamous cell carcinoma * pap smear can detect cervical dysplasia before it progresses * diagnosed via colposcopy and biopsy * lateral invasion can block ureters → renal failure

Answer 184

Invasive Carcinoma

Question 185

Reproductive Pathology: * also known as premature ovarian failure * premature atresia of ovarian follicles in women of reproductive age * most often idiopathic * associated with chromosomal abnormalities (especially in females \< 30 years) * need karyotype screening * patients present with signs of menopause after puberty but before age 40 * ↓ estrogen, ↑ LH, ↑ FSH

Answer 185

Primary Ovarian Insufficiency

Question 186

Most Common Causes of Anovulation

Answer 186

* pregnancy * PCOS * obesity * HPO axis abnormalities * premature ovarian failure * hyperprolactinemia * thyroid disorders * eating disorders * competitive athletics * Cushing syndrome * adrenal insufficiency * chromosomal abnormalities (eg. Turner syndrome)

Question 187

Reproductive Pathology: * also known as Stein-Leventhal syndrome * hyperinsulinemia and/or insulin resistance are hypothesized to alter hypothalamic hormonal feedback response → ↑ LH:FSH, ↑ androgens (eg. testosterone) from theca interna cells, ↓ rate of follicular maturation → unruptured follicles (cysts) + anovulation * common cause of ↓ fertility in women * enlarged, bilateral cystic ovaries * presents with amenorrhea/oligomenorrhea, hirsutism, acne, and ↓ fertility * associated with obesity * ↑ risk of endometrial cancer 2° to unopposed estrogen from repeated anovulatory cycles * Treatment: * cycle regulation via weight reduction (↓ peripheral estrone formation) and OCPs (prevent endometrial hyperplasia due to unopposed estrogen) * Clomiphene and Metformin to induce ovulation * Spironolactone and Ketoconazole (antiandrogens) to treat hirsutism

Answer 187

Polycystic Ovarian Syndrome

Question 188

Ovarian Cysts: * distention of unruptured graafian follicle * may be associated with hyperestrogenism and endometrial hyperplasia * most common ovarian mass in young women

Answer 188

Follicular Cyst

Question 189

Ovarian Cysts: * often bilateral/multiple * due to gonadotropin stimulation * associated with choriocarcinoma and hydatidiform moles

Answer 189

Theca-Lutein Cyst

Question 190

Reproductive Pathology: * most common adnexal mass in women \> 55 years old * can be benign or malignant * arise from surface epithelium, germ cells, or sex cord stromal tissue * majority of malignant tumors are epithelial (serous cystadenocarcinoma most common) * risk ↑with advanced age, infertility, endometriosis, PCOS, genetic predisposition BRCA1 or BRCA2 mutation, Lynch syndrome, and strong family history * risk ↓ with previous pregnancy, history of breastfeeding, OCPs, and tubal ligation * presents with adnexal mass, abdominal distension, bowel obstruction, pleural effusion * monitor response to therapy/relapse by measuring CA 125 levels (not good for screening)

Answer 190

Ovarian Neoplasms

Question 191

Ovarian Neoplasms: * surface epithelium tumor (benign) * most common ovarian neoplasm * lined with fallopian tube–like epithelium * often bilateral

Answer 191

Serous Cystadenoma

Question 192

Ovarian Neoplasms: * surface epithelium tumor (benign) * multiloculated, large * lined by mucus-secreting epithelium

Answer 192

Mucinous Cystadenoma

Question 193

Ovarian Neoplasms: * surface epithelium tumor (benign) * endometriosis within ovary with cyst formation * presents with pelvic pain, dysmenorrhea and dyspareunia * symptoms may vary with menstrual cycle * “Chocolate Cyst” * endometrioma filled with dark, reddish-brown blood * complex mass on ultrasound

Answer 193

Endometrioma

Question 194

Ovarian Neoplasms: * germ cell tumor (benign) * most common ovarian tumor in females 10–30 years old * cystic mass containing elements from all 3 germ layers (eg. teeth, hair, sebum) * can present with pain 2° to ovarian enlargement or torsion * a monodermal form with thyroid tissue (struma ovarii) uncommonly presents with hyperthyroidism

Answer 194

Mature Cystic Teratoma (Dermoid Cyst)

Question 195

Ovarian Neoplasms: * sex cord stromal tumor (benign) * bundles of spindle-shaped fibroblasts * Meigs Syndrome * triad of ovarian fibroma, ascites, and hydrothorax * “pulling” sensation in groin

Answer 195

Fibroma

Question 196

Ovarian Neoplasms: * sex cord stromal tumor (benign) * like granulosa cell tumors, may produce estrogen * usually presents as abnormal uterine bleeding in a postmenopausal woman

Answer 196

Thecoma

Question 197

Ovarian Neoplasms: * resembles bladder epithelium (transitional cell tumor) * solid tumor that is pale yellow-tan and appears encapsulated * “coffee bean” nuclei on H&E stain * usually benign

Answer 197

Brenner Tumor

Question 198

Ovarian Neoplasms: * surface epithelium tumor (malignant) * most common malignant ovarian neoplasm * frequently bilateral * Psammoma bodies

Answer 198

Serous Cystadenocarcinoma

Question 199

Ovarian Neoplasms: * surface epithelium tumor (malignant) * rare malignant mucinous ovarian epithelial tumor * may be metastatic from appendiceal or other GI tumors * can result in pseudomyxoma peritonei—intraperitoneal accumulation of mucinous material

Answer 199

Mucinous Cystadenocarcinoma

Question 200

Ovarian Neoplasms: * germ cell tumor (malignant) * most common in adolescents * equivalent to male seminoma but rarer * 1% of all ovarian tumors * 30% of germ cell tumors * sheets of uniform “fried egg” cells * hCG, LDH = tumor markers

Answer 200

Dysgerminoma

Question 201

Ovarian Neoplasms: * germ cell tumor (malignant) * aggressive * contains fetal tissue, neuroectoderm * commonly diagnosed before age 20 * typically represented by immature/embryonic-like neural tissue

Answer 201

Immature Teratoma

Question 202

Ovarian Neoplasms: * germ cell tumor (malignant) * also known as ovarian endodermal sinus tumor * aggressive * in ovaries or testes and sacrococcygeal area in young children * most common tumor in male infants * yellow, friable (hemorrhagic), solid mass * 50% have Schiller-Duval bodies (resemble glomeruli) * AFP = tumor marker

Answer 202

Yolk Sac Tumor

Question 203

Ovarian Neoplasms: * sex cord stromal tumor (malignant) * most common malignant stromal tumor * predominantly women in their 50s * often produces estrogen and/or progesterone and presents with postmenopausal bleeding, sexual precocity (in pre-adolescents), and breast tendernessh * histology shows Call-Exner bodies (granulosa cells arranged haphazardly around collections of eosinophilic fluid, resembling primordial follicles)

Answer 203

Granulosa Cell Tumor “Give **Gran**ny a **Call**!”

Question 204

Ovarian Neoplasms: * GI malignancy that metastasizes to ovaries → mucin-secreting signet cell adenocarcinoma * commonly presents as bilateral ovarian masses

Answer 204

Krukenberg Tumor

Question 205

Endometrial Conditions: * well-circumscribed collection of endometrial tissue within uterine wall * may contain smooth muscle cells * can extend into endometrial cavity in the form of a polyp * may be asymptomatic or present with painless abnormal uterine bleeding

Answer 205

Polyp

Question 206

Endometrial Conditions: * extension of endometrial tissue (glandular) into uterine myometrium * caused by hyperplasia of basal layer of endometrium * presents with dysmenorrhea, menorrhagia, and uniformly enlarged, soft, globular uterus * Treatment: * GnRH agonists * hysterectomy or excision of an organized adenomyoma

Answer 206

Adenomyosis

Question 207

Endometrial Conditions: * adhesions and/or fibrosis of the endometrium * presents with ↓ fertility, recurrent pregnancy loss, abnormal uterine bleeding, and pelvic pain * often associated with dilation and curettage of intrauterine cavity

Answer 207

Asherman Syndrome

Question 208

Endometrial Conditions: * most common tumor in females * often presents with multiple discrete tumor * ↑ incidence in African Americans * benign smooth muscle tumor * malignant transformation to leiomyosarcoma is rare * estrogen sensitive—tumor size ↑ with pregnancy and ↓ with menopause * peak occurrence at 20–40 years old * may be asymptomatic, cause abnormal uterine bleeding, or result in miscarriage * severe bleeding may lead to iron deficiency anemia * whorled pattern of smooth muscle bundles with well-demarcated borders

Answer 208

Leiomyoma (Fibroid)

Question 209

Endometrial Conditions: * abnormal endometrial gland proliferation usually caused by excess estrogen stimulation * ↑ risk for endometrial carcinoma * nuclear atypia is greater risk factor than complex (vs. simple) architecture * presents as postmenopausal vaginal bleeding * risk factors include anovulatory cycles, hormone replacement therapy, polycystic ovarian syndrome, and granulosa cell tumor

Answer 209

Endometrial Hyperplasia

Question 210

Endometrial Conditions: * most common gynecologic malignancy * peak occurrence at 55–65 years old * presents with vaginal bleeding * typically preceded by endometrial hyperplasia * risk factors include prolonged use of estrogen without progestins, obesity, diabetes, hypertension, nulliparity, late menopause, early menarche, and Lynch syndrome

Answer 210

Endometrial Carcinoma

Question 211

Endometrial Conditions: Inflammation of endometrium D associated with retained products of conception following delivery, miscarriage, abortion, or with foreign body (eg, IUD). Retained material in uterus promotes infection by bacterial flora from vagina or intestinal tract. Chronic endometritis characterized by presence of plasma cells on histology. Treatment: gentamicin + clindamycin +/− ampicillin.

Answer 211

Endometritis

Question 212

Endometrial Conditions: * non-neoplastic endometrium-like glands/stroma outside endometrial cavity * can be found anywhere * most common sites are ovary (frequently bilateral), pelvis, peritoneum * in ovary, appears as endometrioma (blood-filled “chocolate cysts”) * may be due to retrograde flow, metaplastic transformation of multipotent cells, transportation of endometrial tissue via lymphatic system * characterized by cyclic pelvic pain, bleeding, dysmenorrhea, dyspareunia, dyschezia (pain with defecation), and infertility * normal-sized uterus * Treatment: * NSAIDs * continuous OCPs * progestins * GnRH agonists * Danazol * laparoscopic removal

Answer 212

Endometriosis

Question 213

Breast Pathology

Answer 213

Question 214

Benign Breast Disease: * most common in premenopausal women \< 35 years old * present with premenstrual breast pain or lumps * often bilateral and multifocal * nonproliferative lesions include simple cysts (fluid-filled duct dilation, blue dome), papillary apocrine change/metaplasia, and stromal fibrosis * risk of cancer is usually not increased

Answer 214

Fibrocystic Changes

Question 215

Fibrocystic Changes: * acini and stromal fibrosis * associated with calcifications * slight (1.5–2 ×) ↑ risk for cancer

Answer 215

Sclerosing Adenosis

Question 216

Fibrocystic Changes: * cells in terminal ductal or lobular epithelium * ↑ risk of carcinoma with atypical cells

Answer 216

Epithelial Hyperplasia

Question 217

Benign Breast Disease: * inflammatory processes * benign, usually painless, lump due to injury to breast tissue * calcified oil cyst on mammography * necrotic fat and giant cells on biopsy * up to 50% of patients may not report trauma

Answer 217

Fat Necrosis

Question 218

Benign Breast Disease: * inflammatory processes * occurs during breastfeeding * ↑ risk of bacterial infection through cracks in nipple * *S. aureus* is the most common pathogen * treat with antibiotics and continue breastfeeding

Answer 218

Lactational Mastitis

Question 219

Benign Breast Disease: * benign tumor * most common in women \< 35 years old * small, well-defined, mobile mass * ↑ size and tenderness with ↑ estrogen (eg. pregnancy, prior to menstruation) * risk of cancer is usually not increased

Answer 219

Fibroadenoma

Question 220

Benign Breast Disease: * benign tumor * small fibroepithelial tumor within lactiferous ducts, typically beneath areola * most common cause of nipple discharge (serous or bloody) * slight (1.5–2 ×) ↑ risk for cancer

Answer 220

Intraductal Papilloma

Question 221

Benign Breast Disease: * benign tumor * large mass of connective tissue and cysts with “leaf-like” lobulations * most common in 5th decade * some may become malignant

Answer 221

Phyllodes Tumor

Question 222

Benign Breast Disease: * breast enlargement in males due to ↑ estrogen compared with androgen activity * physiologic in newborn, pubertal, and elderly males, but may persist after puberty * other causes include cirrhosis, hypogonadism (eg. Klinefelter syndrome), testicular tumors, and drugs (Spironolactone, hormones, Cimetidine, Finasteride, Ketoconazole)

Answer 222

Gynecomastia **S**ome **H**ormones **C**reate **F**unny **K**nockers. * **S**pironolactone * **H**ormones * **C**imetidine * **F**inasteride * **K**etoconazole

Question 223

Malignant Breast Tumors

Answer 223

* commonly postmenopausal * usually arise from terminal duct lobular unit * amplification/ overexpression of estrogen/progesterone receptors or c-erbB2 (HER-2, an EGF receptor) is common * triple negative (ER ⊝, PR ⊝, and Her2/Neu ⊝) more aggressive * type affects therapy and prognosis * axillary lymph node involvement indicating metastasis is the most important prognostic factor in early-stage disease * most often located in upper-outer quadrant of breast. * Risk Factors: * ↑ estrogen exposure * ↑ total number of menstrual cycles * older age at 1st live birth, * obesity (↑ estrogen exposure as adipose tissue converts androstenedione to estrone) * BRCA1 or BRCA2 gene mutations * African American ethnicity (↑ risk for triple ⊝ breast cancer)

Question 224

Malignant Breast Tumors: * noninvasive * fills ductal lumen * arises from ductal atypia * often seen early as microcalcifications on mammography * early malignancy without basement membrane penetration

Answer 224

Ductal Carcinoma in situ

Question 225

Malignant Breast Tumors: * noninvasive * ductal, central necrosis * subtype of DCIS

Answer 225

Comedocarcinoma

Question 226

Malignant Breast Tumors: * noninvasive * results from underlying DCIS or invasive breast cancer * eczematous patches on nipple * Paget cells = intraepithelial adenocarcinoma cells

Answer 226

Paget Disease

Question 227

Malignant Breast Tumors: * invasive * firm, fibrous, “rock-hard” mass with sharp margins and small, glandular, duct-like cells * tumor can deform suspensory ligaments → dimpling of skin * Classic Morphology: “stellate” infiltration * most common (∼ 75% of all breast cancers)

Answer 227

Invasive Ductal Carcinoma

Question 228

Malignant Breast Tumors: * invasive * orderly row of cells (“single file”), due to ↓ E-cadherin expression * often bilateral with multiple lesions in the same location

Answer 228

Invasive Lobular Carcinoma **L**ines of cells = **L**obular

Question 229

Malignant Breast Tumors: * invasive * fleshy, cellular, lymphocytic infiltrate * good prognosis

Answer 229

Medullary Carcinoma

Question 230

Malignant Breast Tumors: * invasive * dermal lymphatic invasion by breast carcinoma * peau d’orange—skin texture resembles orange peel due to edema leading to tightening of Cooper’s suspensory ligament * neoplastic cells * block lymphatic drainage * poor prognosis (50% survival at 5 years) * often mistaken for mastitis or Paget disease

Answer 230

Inflammatory Breast Cancer

Question 231

Penile Pathology: * abnormal curvature of penis due to fibrous plaque within tunica albuginea * associated with erectile dysfunction * can cause pain and anxiety * consider surgical repair once curvature stabilizes * distinct from penile fracture (rupture of corpora cavernosa due to forced bending)

Answer 231

Peyronie Disease

Question 232

Penile Pathology: * painful sustained erection lasting \> 4 hours * associated with sickle cell disease (sickled RBCs block venous drainage of corpus cavernosum vascular channels), medications (eg. Sldenafil, Trazodone) * treat immediately with corporal aspiration, intracavernosal phenylephrine, or surgical decompression to prevent ischemia

Answer 232

Ischemic Priapism

Question 233

Penile Pathology: * more common in Asia, Africa, and South America * Precursor in situ lesions: * Bowen disease (in penile shaft, presents as leukoplakia) * erythroplasia of Queyrat (carcinoma in situ of the glans, presents as erythroplakia) * Bowenoid papulosis (carcinoma in situ of unclear malignant potential, presenting as reddish papules) * associated with uncircumcised males and HPV

Answer 233

Squamous Cell Carcinoma

Question 234

Reproductive Pathology: * undescended testis (one or both) * impaired spermatogenesis (since sperm develop best at temperatures \< 37°C) * can have normal testosterone levels (Leydig cells are mostly unaffected by temperature) * associated with ↑ risk of germ cell tumors * prematurity ↑ risk * ↓ inhibin B, ↑ FSH, ↑ LH * testosterone ↓ in bilateral cases, normal in unilateral

Answer 234

Cryptorchidism

Question 235

Reproductive Pathology: * rotation of testicle around spermatic cord and vascular pedicle * commonly presents in males 12–18 years old * characterized by acute, severe pain, high-riding testis, and absent cremasteric reflex * Treatment: * surgical correction (orchiopexy) within 6 hours * manual detorsion if surgical option unavailable in timeframe * if testis is not viable, orchiectomy * orchiopexy, when performed, should be bilateral because the contralateral testis is at risk for subsequent torsion

Answer 235

Testicular Torsion

Question 236

Reproductive Pathology: * dilated veins in pampiniform plexus due to ↑ venous pressure * most common cause of scrotal enlargement in adult males * most often on left side because of ↑ resistance to flow from left gonadal vein drainage into left renal vein * can cause infertility because of ↑ temperature * diagnosed by standing clinical exam/Valsalva maneuver (distension on inspection and “bag of worms” on palpation; augmented by Valsalva) or ultrasound with Doppler * does not transilluminate * Treatment: * consider surgical ligation or embolization if associated with pain or infertility

Answer 236

Varicocele

Question 237

Reproductive Pathology: * arise in midline locations * in adults, most commonly in retroperitoneum, mediastinum, pineal, and suprasellar regions * in infants and young children, sacrococcygeal teratomas are most common

Answer 237

Extragonadal Germ Cell Tumors

Question 238

\_\_\_\_\_ are benign lesions that present as testicular masses that can be transilluminated (vs. solid testicular tumors).

Answer 238

Scrotal Masses

Question 239

Scrotal Masses: * common cause of scrotal swelling in infants * due to incomplete obliteration of processus vaginalis * most spontaneously resolve by 1 year old * transilluminating swelling

Answer 239

Congenital Hydrocele

Question 240

Scrotal Masses: * scrotal fluid collection usually 2° to infection, trauma, or tumor * if bloody → hematocele

Answer 240

Acquired Hydrocele

Question 241

Scrotal Masses: * cyst due to dilated epididymal duct or rete testis * paratesticular fluctuant nodule

Answer 241

Spermatocele

Question 242

Reproductive Pathology: * ∼ 95% of all testicular tumors * most often occur in young men * Risk Factors: * cryptorchidism * Klinefelter syndrome * can present as a mixed germ cell tumor * do not transilluminate * usually not biopsied (risk of seeding scrotum) * removed via radical orchiectomy

Answer 242

Testicular Germ Cell Tumors

Question 243

Testicular Germ Cell Tumors: * malignant * painless, homogenous testicular enlargement; * most common testicular tumor * does not occur in infancy * large cells in lobules with watery cytoplasm and “fried egg” appearance * ↑ placental ALP * highly radiosensitive * late metastasis * excellent prognosis * similar to dysgerminoma in females

Answer 243

Seminoma

Question 244

Testicular Germ Cell Tumors: * also known as testicular endodermal sinus tumor * yellow, mucinous * aggressive malignancy of testes, analogous to ovarian yolk sac tumor * Schiller-Duval bodies resemble primitive glomeruli * ↑ AFP is highly characteristic * most common testicular tumor in boys \< 3 years old

Answer 244

Yolk Sac Tumor

Question 245

Testicular Germ Cell Tumors: * malignant * ↑ hCG * disordered syncytiotrophoblastic and cytotrophoblastic elements * hematogenous metastases to lungs and brain * may produce gynecomastia, symptoms of hyperthyroidism (α-subunit of hCG is structurally similar to LH, FSH, TSH)

Answer 245

Choriocarcinoma

Question 246

Testicular Germ Cell Tumors: * unlike in females, mature _____ in adult males may be malignant * benign in children

Answer 246

Teratoma

Question 247

Testicular Germ Cell Tumors: * malignant, hemorrhagic mass with necrosis * painful * worse prognosis than seminoma * often glandular/papillary morphology * “pure” _____ is rare * most commonly mixed with other tumor types * may be associated with ↑ hCG and normal AFP levels when pure (↑ AFP when mixed)

Answer 247

Embryonal Carcinoma

Question 248

Reproductive Pathology: * 5% of all testicular tumors * mostly benign

Answer 248

Testicular Non–Germ Cell Tumors

Question 249

Testicular Non–Germ Cell Tumors: * golden brown color * contains Reinke crystals (eosinophilic cytoplasmic inclusions) * produces androgens or estrogens → gynecomastia in men, precocious puberty in boys

Answer 249

Leydig Cell Tumor

Question 250

Testicular Non–Germ Cell Tumors: androblastoma from sex cord stroma

Answer 250

Sertoli Cell Tumor

Question 251

Testicular Non–Germ Cell Tumors: * most common testicular cancer in older men * not a 1° cancer * arises from metastatic lymphoma to testes * aggressive

Answer 251

Testicular Lymphoma

Question 252

Reproductive Pathology: * common in men \> 50 years old * characterized by smooth, elastic, firm nodular enlargement (hyperplasia not hypertrophy) of periurethral (lateral and middle) lobes, which compress the urethra into a vertical slit * not premalignant * often presents with ↑ frequency of urination, nocturia, difficulty starting and stopping urine stream, and dysuria * may lead to distention and hypertrophy of bladder, hydronephrosis, and UTIs * ↑ free prostate-specific antigen (PSA). * Treatment: * α1-antagonists (Terazosin, Tamsulosin), which cause relaxation of smooth muscle * 5α-reductase inhibitors (eg. Finasteride) * PDE-5 inhibitors (eg. Tadalafil) * surgical resection (eg. TURP, ablation)

Answer 252

Benign Prostatic Hyperplasia

Question 253

Reproductive Pathology: * characterized by dysuria, frequency, urgency, and low back pain * warm, tender, enlarged prostate * Acute * in older men most common bacterium is *E. coli* * in young males consider *C. trachomatis* and *N. gonorrhoeae* * Chronic * either bacterial or nonbacterial (eg. 2° to previous infection, nerve problems, chemical irritation)

Answer 253

Prostatitis

Question 254

Reproductive Pathology: * common in men \> 50 years old * arises most often from posterior lobe (peripheral zone) of prostate gland and is most frequently diagnosed by ↑ PSA and subsequent needle core biopsies * prostatic acid phosphatase (PAP) and PSA are useful tumor markers (↑ total PSA, with ↓ fraction of free PSA) * osteoblastic metastases in bone may develop in late stages, as indicated by lower back pain and ↑ serum ALP and PSA

Answer 254

Prostatic Adenocarcinoma

Question 255

Control of Reproductive Hormones

Answer 255

Question 256

Reproductive Drugs: * GnRH analog with agonist properties when used in pulsatile fashion * antagonist properties when used in continuous fashion (downregulates GnRH receptor in pituitary → ↓ FSH and ↓ LH) * used for uterine fibroids, endometriosis, precocious puberty, prostate cancer, and infertility * causes hypogonadism, ↓ libido, erectile dysfunction, nausea, and vomiting

Answer 256

Leuprolide **Leu**prolide can be used in **lieu** of GnRH.

Question 257

Estrogens

Answer 257

* Ethinyl Estradiol * DES * Mestranol

Question 258

Reproductive Drugs: * bind estrogen receptors * used for ypogonadism or ovarian failure, menstrual abnormalities (combined OCPs), and hormone replacement therapy in postmenopausal women * causes ↑ risk of endometrial cancer (when given without progesterone), bleeding in postmenopausa women, clear cell adenocarcinoma of vagina in females exposed to DES in utero, ↑ risk of thrombi * Contraindications: * ER ⊕ breast cancer * history of DVTs * tobacco use in women \> 35 years old

Answer 258

Estrogens

Question 259

Selective Estrogen Receptor Modulators: * antagonist at estrogen receptors in hypothalamus * prevents normal feedback inhibition and ↑ release of LH and FSH from pituitary, which stimulates ovulation * used to treat infertility due to anovulation (eg. PCOS) * SERMs may cause hot flashes, ovarian enlargement, multiple simultaneous pregnancies, and visual disturbances

Answer 259

Clomiphene

Question 260

Selective Estrogen Receptor Modulators: * antagonist at breast * agonist at bone and uterus * ↑ risk of thromboembolic events and endometrial cancer * used to treat and prevent recurrence of ER/PR ⊕ breast cancer

Answer 260

Tamoxifen

Question 261

Selective Estrogen Receptor Modulators: * antagonist at breast and uterus * agonist at bone * ↑ risk of thromboembolic events but no increased risk of endometrial cancer (vs. Tamoxifen) * used primarily to treat osteoporosis

Answer 261

Raloxifene

Question 262

Aromatase Inhibitors

Answer 262

* Anastrozole * Letrozole * Exemestane

Question 263

Reproductive Drugs: * inhibit peripheral conversion of androgens to estrogen * used for ⊕ breast cancer in postmenopausal women

Answer 263

Aromatase Inhibitors

Question 264

Reproductive Drugs: * used for relief or prevention of menopausal symptoms (eg. hot flashes, vaginal atrophy) and osteoporosis (↑ estrogen, ↓ osteoclast activity) * unopposed estrogen replacement therapy ↑ risk of endometrial cancer, progesterone/progestin is added * possible increased cardiovascular risk

Answer 264

Hormone Replacement Therapy

Question 265

Progestins

Answer 265

* Levonorgestrel * Medroxyprogesterone * Etonogestrel * Norethindrone * Megestrol

Question 266

Reproductive Drugs: * bind progesterone receptors * ↓ growth and ↑ vascularization of endometrium, thicken cervical mucus * used in contraception (forms include pill, intrauterine device, implant, depot injection), endometrial cancer, abnormal uterine bleeding

Answer 266

Progestins Progestin Challenge * presence of withdrawal bleeding excludes anatomic defects (eg. Asherman syndrome) and chronic anovulation without estrogen

Question 267

Antiprogestins

Answer 267

* Mifepristone * Ulipristal

Question 268

Reproductive Drugs: * competitive inhibitors of progestins at progesterone receptors * used for termination of pregnancy (Mifepristone with Misoprostol) and emergency contraception (ulipristal)

Answer 268

Antiprogestins

Question 269

Reproductive Drugs: * forms include pill, patch, and vaginal ring * estrogen and progestins inhibit LH/FSH and thus prevent estrogen surge * no estrogen surge → no LH surge → no ovulation * progestins cause thickening of cervical mucus, thereby limiting access of sperm to uterus * progestins also inhibit endometrial proliferation → endometrium is less suitable to the implantation of an embryo * Contraindications: * smokers \> 35 years old (↑ risk of cardiovascular events) * patients with ↑ risk of cardiovascular disease (including history of venous thromboembolism, coronary artery disease, stroke) * migraine (especially with aura) * breast cancer * liver disease

Answer 269

Combined Contraception * Progestins + Ethinyl Estradiol

Question 270

Reproductive Drugs: * produces local inflammatory reaction toxic to sperm and ova, preventing fertilization and implantation * hormone free * used for long-acting reversible contraception * most effective emergency contraception * causes heavier or longer menses, and dysmenorrhea * risk of PID with insertion (contraindicated in active pelvic infection)

Answer 270

Copper Intrauterine Device

Question 271

Reproductive Drugs: * medications that relax the uterus * include Terbutaline (β2-agonist action), Nifedipine (Ca²⁺ channel blocker), and Indomethacin (NSAID) * used to ↓ contraction frequency in preterm labor and allow time for administration of steroids (to promote fetal lung maturity) or transfer to appropriate medical center with obstetrical care

Answer 271

Tocolytics

Question 272

Reproductive Drugs: * synthetic androgen that acts as partial agonist at androgen receptors * used for endometriosis and hereditary angioedema * causes weight gain, edema, acne, hirsutism, masculinization, ↓ HDL levels, hepatotoxicity, and pseudotumor cerebri

Answer 272

Danazol

Question 273

Reproductive Drugs: * agonists at androgen receptors * used to treat hypogonadism and promote development of 2° sex characteristics * stimulate anabolism to promote recovery after burn or injury * causes masculinization in females and ↓ intratesticular testosterone in males by inhibiting release of LH (via negative feedback) → gonadal atrophy * premature closure of epiphyseal plates * ↑ LDL, ↓ HDL

Answer 273

* Testosterone * Methyltestosterone

Question 274

Antiandrogens: * 5α-reductase inhibitor (↓ conversion of testosterone to DHT) * used for BPH and male-pattern baldness * causes gynecomastia and sexual dysfunction

Answer 274

Finasteride

Question 275

Antiandrogens: * nonsteroidal competitive inhibitor at androgen receptors * used for prostate carcinoma

Answer 275

Flutamide

Question 276

Antiandrogens: * inhibits steroid synthesis (inhibits 17,20 desmolase/17α-hydroxylase) * used in PCOS to reduce androgenic symptoms * can cause gynecomastia and amenorrhea

Answer 276

Ketoconazole

Question 277

Antiandrogens: * inhibits steroid binding (inhibits 17,20 desmolase/17α-hydroxylase) * used in PCOS to reduce androgenic symptoms * can cause gynecomastia and amenorrhea

Answer 277

Spironolactone

Question 278

Reproductive Drugs: * α1-antagonist used to treat BPH by inhibiting smooth muscle contraction * selective for α_1A/D receptors (found on prostate) vs. vascular α1B receptors

Answer 278

Tamsulosin

Question 279

Phosphodiesterase Type 5 Inhibitors

Answer 279

* Sildenafil * Vardenafil * Tadalafil

Question 280

Reproductive Drugs: * inhibit PDE-5 → ↑ cGMP ↑ prolonged smooth muscle relaxation in response to NO → ↑ blood flow in corpus cavernosum of penis, ↓ pulmonary vascular resistance * used for erectile dysfunction, pulmonary hypertension, and BPH (Tadalafil only) * causes headache, flushing, dyspepsia, and cyanopia (blue-tinted vision) * risk of life-threatening hypotension in patients taking nitrates

Answer 280

Phosphodiesterase Type 5 Inhibitors Sildena**fil**, Vardena**fil**, and Tadala**fil** **fill** the penis. “**H**ot and sweaty,” but then **H**eadache, **H**eartburn, and **H**ypotension.

Question 281

Reproductive Drugs: * direct arteriolar vasodilator * used for androgenetic alopecia (pattern baldness) and severe refractory hypertension

Answer 281

Minoxidil